We propose to investigate the areas deemed most promising for providing an integrated synthesis of the fundamental mechanisms of hypertension. We regard the following constellation of factore: 1) Renal humoral agents and renal handling of Na; 2) Body Na, ECF and blood volume; 3) Cardiac output; 4) Brain control of Na, volume, and the circulation as an interrelated xis affecting 5) The caliber of peripheral resistance vessels n normotension and hypertension. All projects will attempt to gain knowledge concerning this constellation. We will study: a) A circulating humoral vasoconstrictive agent in hypertensivd Dahl "S" rats, as to its cause,identity, and source; b) a humoral anti-natriuretic agent in "S" rats; c) Therelationship of specific brain areas to Dahl hypertension and to natriuresis; d) Body Na in Dahl rats after 3 days of salt feeding; e) The effect of beta-blockers on Dahl hypertension; f) The relationship of renal arachidonic acid metabolism to prostaglandins and hypertension; g) Diabetic patients with the low renin, low aldosterone syndrome before and after kidney transplantation; H) The prostaglandins of renal interstitial cells and endothelial cells grown in tissue culture under various c nditi ns; i) The effect f Mg and Li infusi ns n PGE2; j) The effect kf prostaglandin depletion on blkod pressure and vascular responsivity; k) The urinary PGE2 in pre-eclampic women; 1) The relation of prostaglandins to serum osmolality; m) The effect of anti-hypertensive and vasodilator drugs on the caliber nd compliance of arteries; n) PGE2 in quick-frozen Dahl papillas and in Dahl urine will be compared; o) PGH2 will be infused into kidneys to prevent the full rise in papillary Na after indkmethacin; p) Can chronic thiazide shift the pressure natriuresis curve in "s" q) Is papillary Na diminshed in hypertensive "S" rats? r) Does thromboxane constrict renal cortical vessels during hypertonic saline? s) What is the effect of salr feeding on autoregulation of "S" and "R" kidneys? t) The effect on renin of sympathetic nerve stimulation, baroreceptor stimulation, Na depletion will be studied, as will the effect of prostaglandins and angiotensin on the renal and mesenteric vascular beds in early and late Goldblatt hypertension.